The early RNA decay factor ZC3H18 directs first intron splicing.

ZC3H18 interacts with splicing factors to stimulate first intron splicing in human cells, and disruption of the CBC-ARS2-ZC3H18 axis corrupts this process.

• Why it matters: Understanding how the cap-binding complex (CBC) orchestrates both splicing and RNA decay is crucial for elucidating gene expression regulation, yet the mechanism remains unknown.
• What they did: The study used genome-wide analysis to show that ZC3H18 binds to splicing factors PRPF40A, PRP4K, and FNBP4, and that disrupting the CBC-ARS2-ZC3H18 axis impairs first intron splicing.
• The result: Findings suggest that splicing factors displace ZC3H18 from NEXT, favoring productive splicing over RNA decay, thereby mechanistically linking cap-stimulated splicing to RNA decay pathways.